Fabrication processes of porous polymers for tissue engineering scaffolds include fiber bonding, solvent casting, phase separation, and gas foaming combined with particulate leaching. The fiber bonding method uses fibers dispersed in a polymer solution to form a three-dimensional mesh. Solvent casting involves dissolving water-soluble salt in polymer solutions. After evaporation of the solvent, the polymer-salt composite is leached in water to remove the salt particles. Phase separation techniques use emulsification and freeze-drying to create porous structures. Polymer is first dissolved in an organic solvent with distilled water to form an emulsion. The mixture is then cast into a mold and quenched in liquid nitrogen. After the removal of the dispersed water and polymer solvents, a highly porous scaffold can be obtained.
All the above methods require the use of organic solvents, which may never be fully removed even after leaching for several hours. Residual solvents have been a concern for biomedical applications because of their adverse effects on biological cells. In order to eliminate the use of organic solvents in the scaffold-making process, gas foaming combined with particulate leaching was introduced. In the gas foaming process, polymer powder is mixed with salt particles and compression molded into samples of solid discs. The samples are then saturated with CO2 at 800 psi and foamed by releasing the pressure to ambient pressure. The salt particles are subsequently leached out in distilled water. The drawback of this technique is the long leaching time and potential residual salt effect on biological cells.
In addition to the concerns of organic solvents and long leaching periods, all the above methods can only produce porous structures with pores on a single length scale. Not much control is available for creating pores on multiple length scales in the same porous construct. In the particulate leaching approach, the polymer can be mixed with different sized particles to generate pores of different sizes. However, the location of these particles can not be controlled. Solid free form fabrication (SFF) methods, such as selective laser sintering, have the potential to fabricate structures at multiple length scales. However, the resolutions of these methods are not high enough to achieve tissue mimicking architectures. The challenge for fabricating tissue engineering scaffolds with varying morphology at different locations is twofold: 1) it is technically difficult for a single technique to produce porous features on multiple length scales; and 2) the fabrication process should be biocompatible, so as not introduce any harmful substance that could damage the cell's ability to grow and reform tissue.